Perfil epidemiológico de los ingresos involuntarios en el Servicio de Psiquiatría del Hospital Universitario de Gran Canaria Doctor Negrín / Epidemiological profile of involuntary admission in the Psychiatry Service of The University Hospital of Gran Canaria Doctor Negrin

Introducción los ingresos involuntarios por razón de trastorno psíquico se producen con relativa asiduidad en las unidades de internamiento hospitalarias de nuestro país. Este trabajo someterá a estudio las características socio-demográficas y clínicas que se encuentran en relación con este tipo de pacientes, para disponer de más información, tanto clínica como legal, con la que trabajar y desempeñar una mejor función, administración de recursos y desarrollo de habilidades necesarias ante estas situaciones. Material y métodos estudio observacional descriptivo retrospectivo, en el cual se analizarán diferentes variables, seleccionadas previamente, presentes en la población de pacientes psiquiátricos ingresados involuntariamente en el Hospital Doctor Negrín en un período de tiempo de 2 años, 2019 y 2020, determinando así el grado de prevalencia de cada una de ellas. Resultados entre las variables más asociadas al ingreso involuntario se encuentran: ser varón, en la cuarta década de la vida, soltero, sin hijos ni empleo y con un diagnóstico de trastorno psicótico o afectivo mayor que muy probablemente ha abandonado el tratamiento. Discusión sería conveniente hacer un especial seguimiento a los pacientes que cumplan el perfil anteriormente descrito con el objetivo de minimizar la involuntariedad. Es necesario el desarrollo de programas educacionales, de seguimiento y adherencia al alcance de la población de pacientes psiquiátricos para así poder minimizar la necesidad de ingresos involuntarios en nuestro medio. (AU)

Introduction Involuntary admissions due to mental disorders occur with relative regularity in hospital admission units in our country. This work will study the socio-demographic and clinical characteristics found in relation to this type of patients, in order to have more information, both clinical and legal, with which to work and perform a better function, administration of resources and development of necessary skills in these situations. Material and methods Retrospective descriptive observational study, in which different variables will be analyzed, previously selected, present in the population of psychiatric patients involuntarily admitted to the Doctor Negrín Hospital in a period of 2 years, 2019 and 2020, thus determining, the degree of prevalence of each of them. Results Among the variables most associated with involuntary admission are, being a man, in the fourth decade of life, single, without children, or employment, with a diagnosis of major psychotic or affective disorder who has most likely abandoned treatment. Discussion It would be advisable to carry out a special follow-up of patients who meet the profile described above in order to minimize involuntary occurrence. It is necessary to develop educational, follow-up and adherence programs within the reach of the population of psychiatric patients in order to minimize the need for involuntary admissions in our environment. (AU)

Review of pharmacogenomics of psychiatric comorbidities in autism spectrum disorder.

Approximately 70% of individuals diagnosed with autism spectrum disorder (ASD) receive at least one psychotropic medication to treat comorbidities. However, the response to treatment with these drugs is far from satisfactory, with 30-50% of treated patients not responding adequately or developing severe and long-lasting side effects. There is strong evidence of the clinical utility of pharmacogenetics for the personalization of antipsychotic and antidepressant treatments in adult populations. However, the use of pharmacogenetic interventions for the personalization of treatment in ASD populations is minimal. The aim of this review is to summarize the findings of pharmacogenetic studies conducted in subjects with ASD and illustrate their utility in the personalization of treatment with psychoactive drugs in this population group.

Disfonía por tensión muscular: concepto y criterios diagnósticos / Muscle tension dysphonia: concept and diagnostic criteria

Introducción. La disfonía por tensión muscular fue definida, desde 1983, como un desorden que ocasiona un desbalance en las fuerzas de tensión muscular laríngea sin evidencia de patología estructural o neurológica. Denominado también disfonía por tensión muscular, tipo 1, este desorden aún no tiene estandarizadas las características que en la práctica han sido consideradas parte de su diagnóstico.Objetivo. Revisar la información actual, no mayor a cinco años, sobre disfonía por tensión muscular para unificar criterios y diagnósticos actuales.Metodología. Se realizó una búsqueda sistemática a través de las bases de datos PubMed, Google Scholar y Cochrane. Los términos MESH utilizados fueron: dis-fonía por tensión muscular, disfonía funcional, disfonía hipercinética y fatiga vocal. Criterios de inclusión: artículos publicados en revistas arbitradas, sin importancia del diseño y antigüedad no mayor a cinco años. Criterios de exclusión: artículos cuyo enfoque principal no fuera disfonía por tensión muscular y con idioma diferente al inglés o español.Resultados. Dos estudios refieren mayor patología en mujeres que hombres; cuatro investigaciones reportan presión subglótica aumentada (>90 mmHg); tres trabajos reportaron medidas fonatorias; un trabajo propone video de alta resolución como demostración de hiperfunción vocal; una investigación evaluó onda mucosa por elec-troglotografía; una investigación estudió el uso de resonancia magnética funcional; otro trabajo propuso un estudio piloto de evaluación de flujo sanguíneo de músculos infrahioideos. Otro trabajo hace una revisión del uso de métodos diagnósticos.Conclusiones. Los parámetros de mayor peso fueron pico cepstral y presión sub-glótica. Aún es necesario ampliar el conocimiento con nuevas investigaciones que permitan criterios universales

Introduction. Muscle tension dysphonia has been defined since 1983 as a disorder in which there is an imbalance in laryngeal muscle tension forces, without evidence of structural or neurological pathology; it has also been called type I muscle tension dysphonia. The characteristics that in practice have been considered part of the di-agnosis are not standardized.Objective. To review current information, not older than 5 years, on muscle tension dysphonia, unifying current diagnostic criteria.Methodology. A systematic search was carried out through the Pub Med, Google scholar and Cochrane databases. The MESH terms used were: muscle tension dys-phonia, functional dysphonia, hyperkinetic dysphonia, and vocal fatigue. Inclusion criteria: articles published in peer-reviewed journals, regardless of design and pub-lished no more than 5 years before. Exclusion criteria: articles whose main focus was not muscle tension dysphonia and with a language other than English or Spanish.Results. Two studies report more pathology in women than men; four investiga-tions report increased subglottic pressure (> 90 mmHg); three studies reported pho-natory measures; a work proposes high resolution video as a demonstration of vo-cal hyperfunction; an investigation evaluated mucosal wave by electroglottography; an investigation studied the use of functional magnetic resonance imaging; another work proposed a pilot study of infrahyoid muscle blood flow assessment: another work reviews the use of diagnostic methods.Conclusions. The parameters of greater weight were cepstral peak and subglottic pressure. It is still necessary to expand the knowledge with new research that allows universal criteria

[Description of Mycobacterium tuberculosis mutations conferring resistance to rifampicin and isoniazid detected by GenoType® MTBDRplus V.2 in Colombia].

INTRODUCTION: The GenoType®MTBDRplusV.2 assay is a molecular technique endorsed by the World Health Organization and the Pan American Health Organization that allows for the identification of the Mycobacterium tuberculosis complex and the detection of mutations in the rpoß gene for rifampicin resistance, and katG and inhA genes for isoniazid resistance. Due to the genetic variability in the circulating strains around the world, the national tuberculosis control programs should assess the performance of these new diagnostic technologies and their use under program conditions as rapid tests. OBJECTIVE: To describe the mutations identified by the GenoType®MTBDRplusV.2 assay in pulmonary samples and Mycobacterium tuberculosis isolates in the Laboratorio Nacional de Referencia of the Instituto Nacional de Salud in 2014. MATERIALS AND METHODS: We conducted a retrospective, descriptive study to detect the expression of inhA, KatG and rpoß genes, responsible for resistence against isoniazid and rifampicin using the GenoType® MTBDRplus V.2 assay in 837 samples and isolates from tuberculosis cases. RESULTS: Several mutations in the rpoß gene were identified. Ser531Leu was the most frequent (36.6%) followed by Asp516Val (21.6%), while Ser315Thr1 was the most frequent mutation in the katG gene (91.9%). CONCLUSIONS: We were able to identify different mutations present in MDR-TB strains in the country, with frequencies similar to those reported in other countries in the South American region.

Descripción de las mutaciones de Mycobacterium tuberculosis que confieren resistencia a rifampicina e isoniacida detectadas mediante GenoType(r) MTBDR plus V.2 en Colombia / Description of Mycobacterium tuberculosis mutations conferring resistance to rifampicin and isoniazid detected by GenoType(r) MTBDR plus V.2 in Colombia

Resumen Introducción: La metodología de GenoType(r) MTBDRplus V.2 es una técnica molecular aprobada por la Organización Mundial de la Salud y la Organización Panamericana de la Salud para la detección de las mutaciones en el gen rpoβ del complejo Mycobacterium tuberculosis, las cuales confieren resistencia a la rifampicina, y las de los genes katG e inhA que la confieren frente a la isoniacida. Debido a la variación genética en las cepas circulantes a nivel mundial, los programas nacionales de control de la tuberculosis deben comprobar el desempeño de los nuevos métodos de diagnóstico para su aplicación como prueba rápida. Objetivo: Describir las mutaciones detectadas mediante la técnica GenoType(r) MTBDRplus V.2 en muestras pulmonares y aislamientos de M. tuberculosis procesados en el Laboratorio Nacional de Referencia del Instituto Nacional de Salud durante el 2014. Materiales y métodos: Se hizo un estudio retrospectivo descriptivo que determinó la expresión de los genes inhA, KatG y rpoβ responsables de la resistencia a isoniacida y rifampicina, utilizando la técnica GenoType(r) MTBDRplus V.2 en 837 muestras y aislamientos de casos de tuberculosis. Resultados. Se obtuvieron 689 resultados de pruebas: 581(84,3 %) sensibles, 58 (8,4 %) resistentes y 50 (7,2 %) multirresistentes. Se detectaron diversas mutaciones en el gen rpoβ, de las cuales la más frecuente fue la Ser531Leu (36,6 %), seguida por la Asp516Val (21,6 %), en tanto que en el gen katG la más frecuente fue la Ser315Thr1 (91,9 %). Conclusiones: Se detectaron varias mutaciones en los casos resistentes reportados en el país, con frecuencias similares a las reportadas en otros países de la región de América del Sur.

Abstract Introduction: The GenoType(r)MTBDRplusV.2 assay is a molecular technique endorsed by the World Health Organization and the Pan American Health Organization that allows for the identification of the Mycobacterium tuberculosis complex and the detection of mutations in the rpoβ gene for rifampicin resistance, and katG and inhA genes for isoniazid resistance. Due to the genetic variability in the circulating strains around the world, the national tuberculosis control programs should assess the performance of these new diagnostic technologies and their use under program conditions as rapid tests. Objective: To describe the mutations identified by the GenoType(r)MTBDRplusV.2 assay in pulmonary samples and Mycobacterium tuberculosis isolates in the Laboratorio Nacional de Referencia of the Instituto Nacional de Salud in 2014. Materials and methods. We conducted a retrospective, descriptive study to detect the expression of inhA, KatG and rpoβ genes, responsible for resistence against isoniazid and rifampicin using the GenoType(r) MTBDRplus V.2 assay in 837 samples and isolates from tuberculosis cases. Results: Several mutations in the rpoβ gene were identified. Ser531Leu was the most frequent (36.6%) followed by Asp516Val (21.6%), while Ser315Thr1 was the most frequent mutation in the katG gene (91.9%). Conclusions: We were able to identify different mutations present in MDR-TB strains in the country, with frequencies similar to those reported in other countries in the South American region.

Noonan syndrome: lessons learned from genetically modified mouse models.

INTRODUCTION: Noonan syndrome is a RASopathy that results from activating mutations in different members of the RAS/MAPK signaling pathway. At least eleven members of this pathway have been found mutated, PTPN11 being the most frequently mutated gene affecting about 50% of the patients, followed by SOS1 (10%), RAF1 (10%) and KRAS (5%). Recently, even more infrequent mutations have been newly identified by next generation sequencing. This spectrum of mutations leads to a broad variety of clinical symptoms such as cardiopathies, short stature, facial dysmorphia and neurocognitive impairment. The genetic variability of this syndrome makes it difficult to establish a genotype-phenotype correlation, which will greatly help in the clinical management of the patients. Areas covered: Studies performed with different genetically engineered mouse models (GEMMs) developed up to date. Expert commentary: GEMMs have helped us understand the role of some genes and the effect of the different mutations in the development of the syndrome. However, few models have been developed and more characterization of the existing ones should be performed to learn about the impact of the different modifiers in the phenotypes, the potential cancer risk in patients, as well as preventative and therapeutic strategies.

K-Ras(V14I) -induced Noonan syndrome predisposes to tumour development in mice.

The Noonan syndrome (NS) is an autosomal dominant genetic disorder characterized by short stature, craniofacial dysmorphism, and congenital heart defects. A significant proportion of NS patients may also develop myeloproliferative disorders (MPDs), including juvenile myelomonocytic leukaemia (JMML). Surprisingly, scarce information is available in relation to other tumour types in these patients. We have previously developed and characterized a knock-in mouse model that carries one of the most frequent KRAS-NS-related mutations, the K-Ras(V14I) substitution, which recapitulates most of the alterations described in NS patients, including MPDs. The K-Ras(V14I) mutation is a mild activating K-Ras protein; thus, we have used this model to study tumour susceptibility in comparison with mice expressing the classical K-Ras(G12V) oncogene. Interestingly, our studies have shown that these mice display a generalized tumour predisposition and not just MPDs. In fact, we have observed that the K-Ras(V14I) mutation is capable of cooperating with the p16Ink4a/p19Arf and Trp53 tumour suppressors, as well as with other risk factors such as pancreatitis, thereby leading to a higher cancer incidence. In conclusion, our results illustrate that the K-Ras(V14I) activating protein is able to induce cancer, although at a much lower level than the classical K-Ras(G12V) oncogene, and that it can be significantly modulated by both genetic and non-genetic events. Copyright © 2016 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Infective Dermatitis in an Adult Patient With HTLV-1.

Infective dermatitis is a chronic exudative eczematous eruption presenting in human T-lymphotropic virus type 1 (HTLV-1)-infected people. It presents with relapsing erythematous, scaly, and crusted lesions affecting simultaneously the scalp, external ear, retroauricular area, eyelid, paranasal skin, neck axilla, and groin. Superimposed Staphylococcus and Streptococcus infection are common. It mainly affects children and exceptionally adults, and there are only a few published cases. The authors present the first reported case in Paraguay of an adult patient who had symptoms of human T-lymphotropic virus type 1-associated progressive tropical spastic paraparesis, and 6 years after the onset of the neurological symptoms, the patient developed infective dermatitis lesions on the skin, with frequent exacerbations since then.

Loss of p53 induces cell proliferation via Ras-independent activation of the Raf/Mek/Erk signaling pathway.

The Ras family of small GTPases constitutes a central node in the transmission of mitogenic stimuli to the cell cycle machinery. The ultimate receptor of these mitogenic signals is the retinoblastoma (Rb) family of pocket proteins, whose inactivation is a required step to license cell proliferation. However, little is known regarding the molecular events that connect Ras signaling with the cell cycle. Here, we provide genetic evidence to illustrate that the p53/p21 Cdk-interacting protein 1 (Cip1)/Rb axis is an essential component of the Ras signaling pathway. Indeed, knockdown of p53, p21Cip1, or Rb restores proliferative properties in cells arrested by ablation of the three Ras loci, H-, N- and K-Ras. Ras signaling selectively inactivates p53-mediated induction of p21Cip1 expression by inhibiting acetylation of specific lysine residues in the p53 DNA binding domain. Proliferation of cells lacking both Ras proteins and p53 can be prevented by reexpression of the human p53 ortholog, provided that it retains an active DNA binding domain and an intact lysine residue at position 164. These results unveil a previously unidentified role for p53 in preventing cell proliferation under unfavorable mitogenic conditions. Moreover, we provide evidence that cells lacking Ras and p53 proteins owe their proliferative properties to the unexpected retroactivation of the Raf/Mek/Erk cascade by a Ras-independent mechanism.

Sensing with magnetic dipolar resonances in semiconductor nanospheres.

In this work we propose two novel sensing principles of detection that exploit the magnetic dipolar Mie resonance in high-refractive-index dielectric nanospheres. In particular, we theoretically investigate the spectral evolution of the extinction and scattering cross sections of these nanospheres as a function of the refractive index of the external medium (next). Unlike resonances in plasmonic nanospheres, the spectral position of magnetic resonances in high-refractive-index nanospheres barely shifts as next changes. Nevertheless, there is a drastic reduction in the extinction cross section of the nanospheres when next increases, especially in the magnetic dipolar spectral region, which is accompanied with remarkable variations in the radiation patterns. Thanks to these changes, we propose two new sensing parameters, which are based on the detection of: i) the intensity variations in the transmitted or backscattered radiation by the dielectric nanospheres at the magnetic dipole resonant frequency, and ii) the changes in the radiation pattern at the frequency that satisfies Kerker's condition of near-zero forward radiation. To optimize the sensitivity, we consider several semiconductor materials and particles sizes.

Clinical significance of Candida colonization of intravascular catheters in the absence of documented candidemia.

In order to assess the significance of Candida colonization of intravascular catheters (IVC) in patients without documented candidemia, we retrospectively reviewed all Candida-positive IVC tip cultures over a 4-year period. Cases were defined as those with a culture yielding ≥15 colony-forming units of Candida spp. that either did not have blood cultures (BC) taken or had concomitant BC negative for Candida. Patients were followed up until death or 8 months after discharge. Risk factors for poor outcome following IVC removal (death, candidemia, or Candida-related complication) were analyzed. We analyzed a total of 40 patients. Overall mortality was 40.0%, with no death directly attributed to Candida infection. Twenty-two patients received antifungal therapy at the time of IVC removal. Only 1 patient developed a metastatic complication (chorioretinitis) attributable to transient candidemia (2.5% of the global cohort and 3.7% among those with concomitant BC). There were no cases of subsequent candidemia. In the multivariate analysis, the use of antifungal therapy did not show any impact on the risk of poor outcome. The risk of invasive disease in patients with isolated IVC colonization by Candida seems to be low. Nevertheless, the initiation of systemic antifungal therapy should be carefully considered in such context.

Capacidade de limpeza de diferentes soluções irrigantesapós o preparo retrógado com diferentes pontasdiamantadas: análise em MEV / Smear layer presence after apical cavity with diamonds tips and different final irrigants: SEM analysis

O objetivo deste estudo foi avaliar por meioda MEV a presença de smear layer após o preparocavitário apical utilizando diferentes tiposde pontas diamantadas com ultrassom e diferentessoluções irrigantes. Método: Cinquentae seis incisivos inferiores foram submetidos àinstrumentação e obturação, seguido de apicectomiacom broca Zekrya. As raízes foramdivididas em dois grupos: grupo 1 – preparoretrógrado com a ponta final Satelec; grupo 2- preparo retrógrado com ponta CVD. Após opreparo retrógrado, os grupos 1 e 2 foram subdivididosem quatro subgrupos: a) irrigação finalcom EDTA líquido a 17%; b) irrigação final comEDTA gel a 24%; c) irrigação final com ácido cítricoa 50% com tetraciclina e d) irrigação finalcom solução salina. As raízes foram clivadas eas hemissecções foram examinadas através deMEV e determinadas escores de 0 a 3 de acordocom a presença de smear layer. Resultados:Não foi observada diferença significativa entreas pontas diamantadas com relação à presençade smear layer. O ácido cítrico com tetraciclinaa 50% apresentou menor presença de smearlayer, estatisticamente significante da soluçãosalina, enquanto que não houve diferença estatísticaentre as outras soluções. Conclusão: Asolução irrigadora final apresentou influência napresença de smear layer.

The aim of this study was evaluate by SEMthe smear layer presence after apical cavitypreparation using different types of ultrasonicdiamond tip and different final irrigants. Method:Fifty and six root incisors mandibular weresubmitted to instrumentation and obturationfollowed apicectomy with Zekrya bur. The rootswere divided into two groups: group 1 – rootend preparation with Satelec tip; group 2 – rootend preparation with CVD tip. After apical cavitypreparation the groups 1 and 2 were subdividedinto 4 subgroups: a) final irrigation with liquid EDTA at 17%; b) final irrigation with gel EDTA at24%; c) final irrigation with citric acid at 50% withtetracycline and d) final irrigation with saline solution.The roots were cleaved and the hemissectionwere examined through SEM and scored from 0 to3 according to the level of smear layer presence.Results: No significant difference was observedbetween the two types of diamond tips with regardto the smear layer presence. Citric acid 50%with tetracycline contributed to a lesser smear layerpresence and was significantly different from salinesolution. Conclusion: Just the irrigant final had influenceupon the thickness of the smear layer afterapical cavity preparation.

Effect of polarized release of CXC-chemokines from wild-type and cystic fibrosis murine airway epithelial cells.

The respiratory epithelium lining the airway relies on mucociliary clearance and a complex network of inflammatory mediators to protect the lung. Alterations in the composition and volume of the periciliary liquid layer, as occur in cystic fibrosis (CF), lead to impaired mucociliary clearance and persistent airway infection. Moreover, the respiratory epithelium releases chemoattractants after infection, inciting airway inflammation. However, characterizing the inflammatory response of primary human airway epithelial cells to infection can be challenging because of genetic heterogeneity. Using well-characterized, differentiated, primary murine tracheal cells grown at an air-liquid interface, which provides an in vitro polarized epithelial model, we compared inflammatory gene expression and secretion in wild-type and ΔF508 CF airway cells after infection with Pseudomonas aeruginosa. The expression of several CXC-chemokines, including macrophage inflammatory protein-2, small inducible cytokine subfamily member 2, lipopolysaccharide-induced chemokine, and interferon-inducible cytokine-10, was markedly increased after infection, and these proinflammatory mediators were asymmetrically released from the airway epithelium, predominantly from the basolateral surface. Equal amounts of CXC-chemokines were released from wild-type and CF cells. Secreted mediators were concentrated in the thin, periciliary fluid layer, and the dehydrated apical microenvironment of CF airway epithelial cells amplified the inflammatory signal, potentially resulting in high chemokine concentration gradients across the epithelium. Consistent with this observation, the enhanced chemotaxis of wild-type neutrophils was detected in CF airway epithelial cultures, compared with wild-type cells. These data suggest that P. aeruginosa infection of the airway epithelium induces the expression and polarized secretion of CXC-chemokines, and the increased concentration gradient across the CF airway leads to an exaggerated inflammatory response.

Hypoxia-induced autophagy is mediated through hypoxia-inducible factor induction of BNIP3 and BNIP3L via their BH3 domains.

While hypoxia-inducible factor (HIF) is a major actor in the cell survival response to hypoxia, HIF also is associated with cell death. Several studies implicate the HIF-induced putative BH3-only proapoptotic genes bnip3 and bnip3l in hypoxia-mediated cell death. We, like others, do not support this assertion. Here, we clearly demonstrate that the hypoxic microenvironment contributes to survival rather than cell death by inducing autophagy. The ablation of Beclin1, a major actor of autophagy, enhances cell death under hypoxic conditions. In addition, the ablation of BNIP3 and/or BNIP3L triggers cell death, and BNIP3 and BNIP3L are crucial for hypoxia-induced autophagy. First, while the small interfering RNA-mediated ablation of either BNIP3 or BNIP3L has little effect on autophagy, the combined silencing of these two HIF targets suppresses hypoxia-mediated autophagy. Second, the ectopic expression of both BNIP3 and BNIP3L in normoxia activates autophagy. Third, 20-mer BH3 peptides of BNIP3 or BNIP3L are sufficient in initiating autophagy in normoxia. Herein, we propose a model in which the atypical BH3 domains of hypoxia-induced BNIP3/BNIP3L have been designed to induce autophagy by disrupting the Bcl-2-Beclin1 complex without inducing cell death. Hypoxia-induced autophagy via BNIP3 and BNIP3L is clearly a survival mechanism that promotes tumor progression.

Major contribution of MEK1 to the activation of ERK1/ERK2 and to the growth of LS174T colon carcinoma cells.

Mammalian cells express two closely related MEK isoforms, MEK1 and MEK2, upstream of the ERK1/ERK2 MAPK module. Although genetic studies have suggested that MEK1 and MEK2 do not have overlapping functions in vivo, little is known about their specific contribution to the activation of ERKs and to tumor cell proliferation. We used Tet-inducible shRNA to investigate the independent role of MEK1 and MEK2 for the oncogenic and the serum-induced activation of ERK1 and ERK2 in LS174T colon carcinoma cells. We show that MEK1 is the main activator of both ERK1 and ERK2. MEK2 removal has no impact by itself but it can cooperate with MEK1 ablation for the inhibition of ERK1/2 activity. In addition, we show that MEK1 is the critical isoform regulating tumor cell proliferation in vitro and in vivo.

Smurf1 regulates tumor cell plasticity and motility through degradation of RhoA leading to localized inhibition of contractility.

Rho GTPases participate in various cellular processes, including normal and tumor cell migration. It has been reported that RhoA is targeted for degradation at the leading edge of migrating cells by the E3 ubiquitin ligase Smurf1, and that this is required for the formation of protrusions. We report that Smurf1-dependent RhoA degradation in tumor cells results in the down-regulation of Rho kinase (ROCK) activity and myosin light chain 2 (MLC2) phosphorylation at the cell periphery. The localized inhibition of contractile forces is necessary for the formation of lamellipodia and for tumor cell motility in 2D tissue culture assays. In 3D invasion assays, and in in vivo tumor cell migration, the inhibition of Smurf1 induces a mesenchymal-amoeboid-like transition that is associated with a more invasive phenotype. Our results suggest that Smurf1 is a pivotal regulator of tumor cell movement through its regulation of RhoA signaling.

A synthetic, chloride-selective channel that alters chloride transport in epithelial cells.

An Ussing chamber was used to demonstrate that synthetic amphiphilic anion transporters function as chloride transporters in mammalian airway epithelial cells.

Extraordinary optical reflection from sub-wavelength cylinder arrays.

A multiple scattering analysis of the reflectance of a periodic array of sub-wavelength cylinders is presented. The optical properties and their dependence on wavelength, geometrical parameters and cylinder dielectric constant are analytically derived for both s- and p-polarized waves. In absence of Mie resonances and surface (plasmon) modes, and for positive cylinder polarizabilities, the reflectance presents sharp peaks close to the onset of new diffraction modes (Rayleigh frequencies). At the lowest resonance frequency, and in the absence of absorption, the wave is perfectly reflected even for vanishingly small cylinder radii.

Pseudomonas aeruginosa acquires biofilm-like properties within airway epithelial cells.

Pseudomonas aeruginosa can notably cause both acute and chronic infection. While several virulence factors are implicated in the acute phase of infection, advances in understanding bacterial pathogenesis suggest that chronic P. aeruginosa infection is related to biofilm formation. However, the relationship between these two forms of disease is not well understood. Accumulating evidence indicates that, during acute infection, P. aeruginosa enters epithelial cells, a process viewed as either a host-mediated defense response or a pathogenic mechanism to avoid host-mediated killing. We investigated the possibility that epithelial cell entry during early P. aeruginosa-epithelial cell contact favors bacterial survival and is linked to chronic infection. Using electron microscopy and confocal microscopy to analyze primary culture airway epithelial cells infected with P. aeruginosa, we found that epithelial cells developed pod-like clusters of intracellular bacteria with regional variation in protein expression. Extracellular gentamicin added to the medium after acute infection led to the persistence of intracellular P. aeruginosa for at least 3 days. Importantly, compared to bacterial culture under planktonic conditions, the intracellular bacteria were insensitive to growth inhibition or killing by antibiotics that were capable of intraepithelial cell penetration. These findings suggest that P. aeruginosa can use airway epithelial cells as a sanctuary for persistence and develop a reversible antibiotic resistance phenotype characteristic of biofilm physiology that can contribute to development of chronic infection.

Consistencia interna y estructura factorial de un cuestionario sobre autorrealización y crecimiento personal / Reliability and factorial structure of a questionnaire on realization and personal growth

El presente trabajo aporta un instrumento sencillo, fiable e idóneo para la evaluación de valores de realización personal y social en adolescentes. A partir de las respuestas de 1.197 chicos y chicas de 11 a 18 años se analiza la consistencia interna y estructura factorial del cuestionario de Autoconcepto y Realización, AURE, construido para este fin. La configuración resultante se estructura en torno a tres factores esenciales: Afrontamiento, operatividad y realización en el quehacer, que tiene en cuenta la necesidad de ser eficaz y disfrutar afrontando los retos que plantea un proyecto de autorrealización. Autoconcepto y autoestima, factor que implica una dimensión descriptiva y valorativa y que consideramos el eje central del proyecto de autorrealización. Y, por último, el factor Empatía y realización social, como capacidad de disfrute en las relaciones afectivas, actitud de comunicación, inquietud por los problemas de los demás y disposición a colaborar

A simple, reliable instrument, which is suitable for the evaluation of values of personal and social actualization in adolescents, is presented. From the responses of 1,197 boys and girls of between 11 and 18 years old, an analysis is made of the reliability and factorial structure of the Self-concept and Actualisation Questionnaire, AURE, which was drawn up with this aim. The resulting configuration is structured around three fundamental factors: Confrontation, Operation and Actualisation in the task, which includes the necessity to be efficient and to enjoy facing the challenges involved in a self-actualisation project. Secondly Self-concept and Self-esteem which bring a descriptive and affective dimension which is seen here as pivotal to any self-actualisation project. Finally, the factor of Empathy and Social Actualisation, which is the capacity to enjoy caring relationships, attitude towards communication, concern about other people’s problems and willingness to collaborate